Cancers of different localization are widespread and are major cause of mortality of all ages. Tumor growth is a complex multistage process. Occurrence and progressive tumor growth is dependent on both the properties of cancer cells, and the state of immunological reactivity. This determines the diversity of approaches of the cancer therapy using one or several basic methods: surgery, radiotherapy, chemotherapy and immunotherapy. Their goal is to minimize the mass of the tumor. In case of solid tumors, surgical removal of the tumor is the first line option. Leukemia and other generalized diseases are treated by massive radiation or chemotherapy. However, neither method alone is able to eliminate all tumor cells and to achieve a total recovery. Therefore, modern oncology usually applies the combinations of treatments to eliminate the tumor cells.
Unfortunately, in spite of the successful surgical removal of the primary tumor, the likelihood of recurrence is very high, since the tumor is able to spread and metastasize to surrounding tissues and organs. Metastasis begins with local invasion of tumor cells from the primary tumor into the surrounding tissue and cells enter the blood or lymphatic circulation system (Hunter, et al, Breast Cancer Res, 2008, 10, S2; Talmadge et al, Cancer Res 2010, 70, 5649-5669). After removal of the primary tumor the percentage of patients who have diagnosed metastases in various organs is up to 30% (Essner et al, Arch Surg, 2004, 139, 961-966, 966-7).
Metastases are responsive for 90% of deaths from cancer. There are the lymphogenous, hematogenous and mixed (through lymphatic, haematogenous or through seeding) ways of spreading metastasis. Lymphogenous spreading occurs through the lymphatic system, where cancer cells penetrate the lymphatic system and then enter the blood stream. Malignant tumors of internal organs: esophagus, stomach, colon, larynx, cervix—often metastasize to the lymph nodes in this way.
In the case of haematogenous path, the tumor cells penetrate the blood vessel first and then disseminate by blood flow in different organs and tissues (e.g. lungs, liver, bone etc.). Most deaths associated with this pathway, because surgical intervention increases the risk of the spread of tumor cells from the bloodstream. Malignant tumors of the lymphatic and hematopoietic tissue—sarcoma, hypernephroma, horionepitelioma metastasize in this way.
However, most cancers: breast, thyroid, lungs and ovaries—are able to metastasize by lymphogenous and haematogenous equally (Achen, Stacker, Annals of the New York Academy of Sciences, 2008, 1131, pp. 225-234; Li and Li, Int. J. Oncol., 2014, 44, 1806-1812).
Metastatic cancer may be treated with systemic therapy (chemotherapy, biological therapy, targeted therapy, hormonal therapy), local therapy (surgery, radiation therapy), or a combination of these treatments. ([Guideline] Fizazi K, Greco F A, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep. 26 Suppl. 5:v133-8.) Several anticancer drugs like oxaliplatin and irinotecan are used in liver metastasis with some effect. Efficiency of the treatment of metastatic cancer of unknown primary origin with cisplatin and 5-fluorouracil-based chemotherapy is still under debate. The most effective chemotherapy regimens for patients with metastatic cancer of unknown primary origin involve combination therapy with a platinum compound (cisplatin or carboplatin) and a taxane (preferably paclitaxel). However, even this combination gives a response rate only of about 12-26% and a median survival of 5-7 months. Triple drug therapy does not appear to offer any additional benefit (Vajdic C M, Goldstein D. Cancer of unknown primary site. Aust Famr Physician. 2015 September 44 (9):640-3.)
Unfortunately, majority of metastatic cancers are not curable today. For example, metastatic breast cancer treatment can prolong life, delay the progression of the cancer, relieve cancer-related symptoms, and improve quality of life. Nevertheless, the median survival of individuals with metastatic breast cancer is only 18 to 24 months (http://www.uptodate.com/contents/treatment-of-metastatic-breast-cancer-beyond-the-basics). Therefore, there still is high medical need for effective antimetastatic chemotherapeutic medicines.